Abstract

Fatty acids are important sources of energy and are esterified onto glycerol to form triglycerides and phospholipids. The former serve as a transport and storage mechanism for energy in the body while the latter are
structurally crucial for cell membranes. Fatty acids also form esters
with cholesterol which can be stored in cells or be transported in lipoproteins.
<br>Dietary fat is digested to the component fatty acids and cholesterol before
assimilation by the enterocyte which metabolises them to triglyceride and
cholesterol ester before incorporating these into CM. MTP assembles the
lipids on apoB<sub>48</sub>. LPL and Cii are crucial for processing CM and apoE is
necessary to clear CM remnants. Postprandially, triglycerides in CM are
processed rapidly and efficiently. The contribution from dietary cholesterol
to the total plasma cholesterol is small immediately after the meal but regulation of the LDLR results in significant changes over weeks.
<br>The liver sustains plasma triglycerides by the production of VLDL, using apoB&lt;sub&gt;100&lt;/sub&gt; and MTP for assembly. VLDL is metabolised in a similar manner to CM; the VLDL remnants clearing by virtue of apoE. In contrast to CM, a proportion of the VLDL remnants
is metabolised to LDL. LDL carries most of the plasma cholesterol in humans and is cleared by the binding of apoB to the LDLR. It is atherogenic, especially when smaller and denser, a modulation that can happen with mild hypertriglyceridaemia.
<br>Reverse cholesterol transport begins intracellularly with ABC A1 which permits the export onto apoAi and phospholipid complexes. LCAT allows more cholesterol assimilation onto HDL. CETP transfers cholesterol ester
to other lipoproteins for delivery to the liver but cholesterol ester can also be transferred to the liver directly.
<br>Familial hypercholesterolaemia (FH) is
a common metabolic error world-wide and is even more common in several South African communities. It is due to mutations in the LDLR. Heterozygous FH is characterised by an increase in LDLC (>5 mmol/l), tendon xanthomata and premature heart disease. Familial binding defective apoB is phenotypically similar. Familial combined hyperlipidaemia (FCH) is also characterised by dominant inheritance but there may be family members with different hyperlipidaemia patterns and tendon xanthomata are absent. <br>Dysbetalipoproteinaemia is a mixed hyperlipidaemia due to dysfunction of
apoE. Severe hypertriglyceridaemia due to CM accumulation is seen with
homozygous LPL or homozygous apoCii deficiency. When apoB is truncated
to the extent that it cannot assimilate lipid, or when MTP is absent, the failure of CM production causes malabsorption and low postprandial
triglycerides and the failure of VLDL production results in very low
cholesterol concentrations.